Takeo Iwamoto

US Patent:

6750200, Jun 15, 2004

Filed:

Nov 9, 2000

Appl. No.:

09/710419

Inventors:

John M. Tomich - Manhattan KS
Takeo Iwamoto - Manhattan KS
James R. Broughman - Manhattan KS
Bruce D. Schultz - Wamego KS

Assignee:

Kansas State University Research Foundation - Manhattan KS

International Classification:

C12Q 100

US Classification:

514 13, 530300, 530326, 435 4, 435325, 436151, 514 14

Abstract:

The present invention provides a family of peptides based upon the M2GlyR sequence. These peptides are derivatives of the M2GlyR sequence and can be modified at their ends to include a plurality of polar amino acid residues to enhance their solubility. Particularly preferred derivatives include portions of the M2GlyR sequence which are palindromic to another portion of the peptide or to the M2GlyR sequence itself. Preferably these portions are at least 7 amino acid residues in length. Peptides embraced by the present invention are characterized by having greater effects on the transepithelial electrical resistance of cells at lower concentrations. Peptides of the present invention have been shown to increase Isc in MDCK epithelial cell monolayers with half maximal effects observed at or below 30 M, a nearly 10-fold improvement over any peptide previously characterized in the M2GlyR family.

US Patent:

7592341, Sep 22, 2009

Filed:

Dec 15, 2005

Appl. No.:

11/304929

Inventors:

John M. Tomich - Manhattan KS, US
Takeo Iwamoto - Manhattan KS, US

Assignee:

Kansas State University Research Foundation - Manhattan KS

International Classification:

A61K 47/16

US Classification:

514249, 5147723, 514773

Abstract:

Improved methods and preparations are provided for ocular administration of therapeutic drugs. The preparations include respective quantities of a drug and a peptide which enhances transport of the drug across ocular tissues. The drug and peptide components may be separately administered or used as a mixture. The preferred peptide is NC-1059 (SEQ. ID NO. 1).

US Patent:

7745570, Jun 29, 2010

Filed:

Dec 16, 2005

Appl. No.:

11/793187

Inventors:

John Tomich - Manhattan KS, US
Takeo Iwamoto - Manhattan KS, US
Xinchun Shen - Chapel Hill NC, US
Xiuzhi Susan Sun - Manhattan KS, US

Assignee:

Kansas State University Research Foundation - Manhattan KS

International Classification:

C07K 7/00
C07K 14/00

US Classification:

530300

Abstract:

A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

US Patent:

20120021020, Jan 26, 2012

Filed:

Mar 26, 2010

Appl. No.:

13/259771

Inventors:

John M. Tomich - Manhattan KS, US
Takeo Iwamoto - Manhattan KS, US
Yasuaki Hiromasa - Manhattan KS, US
Sushanth Gudlur - Manhattan KS, US

Assignee:

KANSAS STATE UNIVERSITY RESEARCH FOUNDATION - Manhattan KS

International Classification:

A61K 9/00
A61K 38/16
A61K 38/43
A61K 51/12
A61K 31/7088
A61K 38/10
A61K 47/42

US Classification:

424400, 530327, 530326, 530325, 530324, 514773, 424 121, 514 44 R, 424 941

Abstract:

The present invention provides branched amphipathic peptides and vesicles formed thereof. The peptides comprise a polar/positively charged C-terminal segment, a branch point, and two hydrophobic N -terminal segments extending from the branch point. The vesicles are formed using a plurality of first and second peptides, wherein the first peptide has a different chain length from the second peptide. When a plurality of the first and second peptides are mixed together, they self-assemble to form small spheres defined by a membrane consisting of an interlocking peptide network bilayer and having a liquid-receiving interior space (i.e., hollow core). In the bi-layer, the respective hydrophobic segments of the peptides form beta-sheet structures having a hydrogen bond-stabilized, anti-parallel orientation in which the opposed sequences interlock to form a zipper-like structure in three dimensions. Thus, the peptide assembly (i.e., vesicle) can be held together at reduced concentrations where lipid vesicles would breakdown.

US Patent:

59228407, Jul 13, 1999

Filed:

Jul 23, 1996

Appl. No.:

8/685279

Inventors:

John M. Tomich - Manhattan KS
Takeo Iwamoto - Manhattan KS

Assignee:

Kansas State University Research Foundation - Manhattan KS

International Classification:

A61K 3804

US Classification:

530344

Abstract:

Methods for making preparations of homogenous peptides are disclosed. In these methods, reversible alterations of the physicochemical properties of the peptides are exploited. In preferred embodiments, the methods include the following sequential steps: (1) exhaustive capping is carried out during solid-phase synthesis of a desired peptide; (2) a cleavable linker is attached to the peptide, (3) a polymer is added to the peptide either by condensation with preformed polymer or by in situ polymerization such that the linker is interposed between the polymer moiety and the peptide moiety of the resultant adduct; alternatively, steps (2) and (3) can be conducted simultaneously by attaching a combination polymer/linker to the peptide; (4) the polymer-peptide adduct is cleaved from the resin; (5) the polymer-peptide adduct is purified from undesired, nonadducted peptides; and (6) the polymer-peptide adduct is cleaved at the linker, and the desired peptide is purified from the polymer. In some cases, it may be desirable to omit step (6) in order to leave the polymer moiety attached to the desired peptide. For example, the polymer-peptide adducts of the present invention are very soluble in water, and therefore can be used to solubilize amphipathic peptides.

US Patent:

60778261, Jun 20, 2000

Filed:

Jun 8, 1998

Appl. No.:

9/093227

Inventors:

John M. Tomich - Manhattan KS
Takeo Iwamoto - Manhattan KS
Lawrence P. Sullivan - Shawnee KS

Assignee:

Kansas State University Research Foundation - Manhattan KS

International Classification:

C07K 1400
A61K 3816

US Classification:

514 12

Abstract:

The present invention is directed to multiple-peptide channel assemblies for transport of anions such as chloride ions through epithelial cells, synthetic peptides capable of forming such channel assemblies and methods for using channel assemblies in therapeutic contexts for altering the flux of water across epithelial cells. The channel assemblies are composed of a plurality of peptides that transport through the membrane of an epithelial cell and provide for alteration of the flux of water through the cell. The peptides are soluble in water to a level of at least 10 mM and exhibit at least about 50% helical content when dispersed in a 40% trifluoroethanol/60% water solution. The peptides ideally have the amino acid sequence ABC(X). sub. n DEF, where A, B, C, D, F and X are individual amino acid residues, n ranges from 12-24 and at least one of the amino acids selected from the group consisting of A, B, and C is a charged amino acid, and at least one of the amino acids selected from the group consisting of D, E, and F is a charged amino acid. The method hereof provides for altering flux of water from an epithelial cell and includes providing from 3-6 peptides capable of forming a channel assembly with each of such peptides having from about 18-30 amino acid residues therein, then contacting the peptides with a surface of an epithelial cell to cause the peptides to embed therein and alter the flux of water across the cell.